TY - JOUR
T1 - Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction
AU - Gibson, C. Michael
AU - Duffy, Danielle
AU - Korjian, Serge
AU - Bahit, M. Cecilia
AU - Chi, Gerald
AU - Alexander, John H.
AU - Lincoff, A. Michael
AU - Heise, Mark
AU - Tricoci, Pierluigi
AU - Deckelbaum, Lawrence I.
AU - Mears, Sojaita Jenny
AU - Nicolau, Jose C.
AU - Lopes, Renato D.
AU - Merkely, Bela
AU - Lewis, Basil S.
AU - Cornel, Jan H.
AU - Trebacz, Jaroslaw
AU - Parkhomenko, Alexander
AU - Libby, Peter
AU - Sacks, Frank M.
AU - Povsic, Thomas J.
AU - Bonaca, Marc
AU - Goodman, Shaun G.
AU - Bhatt, Deepak L.
AU - Tendera, Michal
AU - Steg, P. Gabriel
AU - Ridker, Paul M.
AU - Aylward, Philip
AU - Kastelein, John J.P.
AU - Bode, Christoph
AU - Mahaffey, Kenneth W.
AU - Nicholls, Stephen J.
AU - Pocock, Stuart J.
AU - Mehran, Roxana
AU - Harrington, Robert A.
AU - AEGIS-II Committees and Investigators
PY - 2024/5/2
Y1 - 2024/5/2
N2 - Background-Cardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux - a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein - has been associated with an increased risk of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the risk of recurrent cardiovascular events after acute myocardial infarction is unclear.Methods-We conducted an international, double-blind, placebo-controlled trial involving patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors. Patients were randomly assigned to receive either four weekly infusions of 6 g of CSL112 or matching placebo, with the first infusion administered within 5 days after the first medical contact for the acute myocardial infarction. The primary end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes from randomization through 90 days of follow-up.Results-A total of 18,219 patients were included in the trial (9112 in the CSL112 group and 9107 in the placebo group). There was no significant difference between the groups in the risk of a primary end-point event at 90 days of follow-up (439 patients [4.8%] in the CSL112 group vs. 472 patients [5.2%] in the placebo group; hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.05; P=0.24), at 180 days of follow-up (622 patients [6.9%] vs. 683 patients [7.6%]; hazard ratio, 0.91; 95% CI, 0.81 to 1.01), or at 365 days of follow-up (885 patients [9.8%] vs. 944 patients [10.5%]; hazard ratio, 0.93; 95% CI, 0.85 to 1.02). The percentage of patients with adverse events was similar in the two groups; a higher number of hypersensitivity events was reported in the CSL112 group.Conclusions-Among patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors, four weekly infusions of CSL112 did not result in a lower risk of myocardial infarction, stroke, or death from cardiovascular causes than placebo through 90 days. (Funded by CSL Behring; AEGIS-II ClinicalTrials.gov number, NCT03473223.)
AB - Background-Cardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux - a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein - has been associated with an increased risk of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the risk of recurrent cardiovascular events after acute myocardial infarction is unclear.Methods-We conducted an international, double-blind, placebo-controlled trial involving patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors. Patients were randomly assigned to receive either four weekly infusions of 6 g of CSL112 or matching placebo, with the first infusion administered within 5 days after the first medical contact for the acute myocardial infarction. The primary end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes from randomization through 90 days of follow-up.Results-A total of 18,219 patients were included in the trial (9112 in the CSL112 group and 9107 in the placebo group). There was no significant difference between the groups in the risk of a primary end-point event at 90 days of follow-up (439 patients [4.8%] in the CSL112 group vs. 472 patients [5.2%] in the placebo group; hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.05; P=0.24), at 180 days of follow-up (622 patients [6.9%] vs. 683 patients [7.6%]; hazard ratio, 0.91; 95% CI, 0.81 to 1.01), or at 365 days of follow-up (885 patients [9.8%] vs. 944 patients [10.5%]; hazard ratio, 0.93; 95% CI, 0.85 to 1.02). The percentage of patients with adverse events was similar in the two groups; a higher number of hypersensitivity events was reported in the CSL112 group.Conclusions-Among patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors, four weekly infusions of CSL112 did not result in a lower risk of myocardial infarction, stroke, or death from cardiovascular causes than placebo through 90 days. (Funded by CSL Behring; AEGIS-II ClinicalTrials.gov number, NCT03473223.)
KW - Acute Coronary Syndromes
KW - Cardiology
KW - Clinical Medicine
KW - Clinical Medicine General
KW - Coronary Disease/Myocardial Infarction
KW - Emergency Medicine
KW - Emergency Medicine General
KW - Lipids
UR - http://www.scopus.com/inward/record.url?scp=85192037946&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2400969
DO - 10.1056/NEJMoa2400969
M3 - Article
C2 - 38587254
AN - SCOPUS:85192037946
SN - 0028-4793
VL - 390
SP - 1560
EP - 1571
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 17
ER -